Trial Outcomes & Findings for Study on the Effect of a Beta Blocker on Increased Sensitivity to Pain in Humans Caused by Opioids (NCT NCT01222091)

Results Overview

A slightly modified version of a previously described model of secondary hyperalgesia was used. Two copper wires contained in a microdialysis catheter were inserted in parallel over a length of 5 mm into the dermis of the right volar forearm. The wires were connected to a constant current stimulator controlled by a pulse generator to deliver rectangular and monophasic pulses with a duration of 0.5 mg at 2 Hz. Over a period of 15 min, the current was increased by targeting a pain rating of 5 on an 11-point numeric rating scale (0 = no pain and 10 = maximum tolerable pain) until the hyperalgesic area surrounding the stimulation site was fully established. Once the area was established, the current was held constant. Percent change from baseline in size (area) of secondary hyperalgesia after cessation of remifentanil infusion was calculated per group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline; 15 min post remifentanil (REM) infusion; 60 min post REM infusion

Results posted on

2018-06-15

Participant Flow

Participant milestones

Participant milestones
Measure	Propranolol, Then Placebo Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.	Placebo, Then Propranolol Half of the participants received saline placebo at the first study session and propranolol at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.
Overall Study STARTED	5	5
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study on the Effect of a Beta Blocker on Increased Sensitivity to Pain in Humans Caused by Opioids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=10 Participants Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.
Age, Continuous	23.8 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Weight	78.8 kilograms n=5 Participants
Height	178 centimeters n=5 Participants

PRIMARY outcome

Timeframe: Baseline; 15 min post remifentanil (REM) infusion; 60 min post REM infusion

A slightly modified version of a previously described model of secondary hyperalgesia was used. Two copper wires contained in a microdialysis catheter were inserted in parallel over a length of 5 mm into the dermis of the right volar forearm. The wires were connected to a constant current stimulator controlled by a pulse generator to deliver rectangular and monophasic pulses with a duration of 0.5 mg at 2 Hz. Over a period of 15 min, the current was increased by targeting a pain rating of 5 on an 11-point numeric rating scale (0 = no pain and 10 = maximum tolerable pain) until the hyperalgesic area surrounding the stimulation site was fully established. Once the area was established, the current was held constant. Percent change from baseline in size (area) of secondary hyperalgesia after cessation of remifentanil infusion was calculated per group.

Outcome measures

Outcome measures
Measure	Propranolol n=10 Participants Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.	Placebo n=10 Participants Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.
Percent Change From Baseline in Size (Area) of Secondary Hyperalgesia After Cessation of Remifentanil Infusion, a Measure of Opioid-induced Hyperalgesia (OIH). 15 min post remifentanil infusion	-28 percentage of change	-34 percentage of change
Percent Change From Baseline in Size (Area) of Secondary Hyperalgesia After Cessation of Remifentanil Infusion, a Measure of Opioid-induced Hyperalgesia (OIH). 60 min post remifentanil infusion	-19 percentage of change	141.5 percentage of change

SECONDARY outcome

Timeframe: Pretreatment [90 min prior to 60-min REM infusion]; 30 min prior to 60-min REM infusion; 15 and 40 min after start of 60-min REM infusion; 5, 15, and 75 minutes after finish of 60-min REM infusion)

OOWS: Is a 13-item instrument of documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score = 13, minimum score = 0. Lower scores correspond to fewer symptoms.

Outcome measures

Outcome measures
Measure	Propranolol n=10 Participants Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.	Placebo n=10 Participants Half of the participants received propranolol at the first study session and the saline placebo at the second session. The treatment infusions were administered continuously before, during, and after remifentanil infusion.
Objective Opioid Withdrawal Scale (OOWS) Pretreatment	1.2 units on a scale Standard Deviation 1.5	1.1 units on a scale Standard Deviation 1.3
Objective Opioid Withdrawal Scale (OOWS) 30 min prior to REM infusion	1.1 units on a scale Standard Deviation 2	1.1 units on a scale Standard Deviation 1
Objective Opioid Withdrawal Scale (OOWS) 15 min after start of REM infusion	0.1 units on a scale Standard Deviation 2	0.8 units on a scale Standard Deviation 1
Objective Opioid Withdrawal Scale (OOWS) 40 min after start of REM infusion	0.8 units on a scale Standard Deviation 2	0.5 units on a scale Standard Deviation 1
Objective Opioid Withdrawal Scale (OOWS) 5 minutes after finish of REM infusion	3 units on a scale Standard Deviation 4	1.8 units on a scale Standard Deviation 2
Objective Opioid Withdrawal Scale (OOWS) 15 minutes after finish of REM infusion	2.8 units on a scale Standard Deviation 4.2	2.1 units on a scale Standard Deviation 2.1
Objective Opioid Withdrawal Scale (OOWS) 75 minutes after finish of REM infusion	1.7 units on a scale Standard Deviation 4	1.6 units on a scale Standard Deviation 2

Adverse Events

Propranolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Larry Chu

Stanford University School of Medicine

Phone: (650) 723-6632

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place